Abstract
The pars tuberalis (PT) is part of the anterior pituitary gland surrounding the median eminence as a thin cell layer. The characteristics of PT differ from those of the pars distalis (PD), such as cell composition and gene expression, suggesting that the PT has a unique physiological function compared to the PD. Because the PT highly expresses melatonin receptor type 1, it is considered a mediator of seasonal and/or circadian signals of melatonin. Expression of neuromedin U (NMU) that is known to regulate energy balance has been previously reported in the rat PT; however, the regulatory mechanism of NMU mRNA expression and secretion in the PT are still obscure. In this study, we examined both the diurnal change of NMU mRNA expression in the rat PT and the effects of melatonin on NMU in vivo. In situ hybridization and quantitative PCR analysis of laser microdissected PT samples revealed that NMU mRNA expression in the PT has diurnal variation that is high during the light phase and low during the dark phase. Furthermore, melatonin administration significantly suppressed NMU mRNA expression in the PT in vivo. On the other hand, 48 h fasting did not have an effect on PT-NMU mRNA expression, and the diurnal change of NMU mRNA expression was maintained. We also found the highest expression of neuromedin U receptor type 2 (NMUR2) mRNA in the third ventricle ependymal cell layer, followed by the arcuate nucleus and the spinal cord. These results suggest that NMU mRNA expression in the PT is downregulated by melatonin during the dark phase and shows diurnal change. Considering that NMU mRNA in the PT showed the highest expression level in the brain, PT-NMU may act on NMUR2 in the brain, especially in the third ventricle ependymal cell layer, with a circadian rhythm.
Highlights
The pars tuberalis (PT), which comprises the rostral part of the anterior pituitary gland surrounding the median eminence as a thin cell layer, has characteristics that differ from those of the pars distalis (PD)
Strong staining for neuromedin U (NMU) mRNA was observed in the PT, and NMU mRNA-expressing cells were widely distributed throughout the PT (Fig. 1A, B)
No signal was detected in any other regions, including the VMH, ARC, and SCN, where NMU mRNA expression has been previously reported in the rat brain using radioisotope-labeled probe [16,30] (Fig. 1A, C)
Summary
The pars tuberalis (PT), which comprises the rostral part of the anterior pituitary gland surrounding the median eminence as a thin cell layer, has characteristics that differ from those of the pars distalis (PD). It has been suggested that TSH secreted from the PT acts on the TSH receptor of the ependymal cell layer of the mediobasal hypothalamus and regulates the expression of type 2 deiodinase, resulting in the regulation of GnRH release in seasonal animals [12,13]. This effect of PT-TSH has been reported in mice, which are non-seasonal breeding animals [14]
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